Brain

Overview

Evaluation of Photic Countermeasures for Circadian Entrainment of Neurobehavioral Performance and Sleep-Wake Regulation Before and During Spaceflight

Principal Investigator:
Charles A. Czeisler, Ph.D., M.D.

Organization:
Harvard-Brigham and Women's Hospital

Bright light is currently used to synchronize crew members’ sleep-wake schedules with variable launch times. However, bright light is unavailable during missions. Recent studies have revealed that shorter wavelength light is effective for sleep cycle phase shifting and for enhancing of alertness and performance.

So Dr. Charles A. Czeisler and colleagues have shown that short-wavelength light in the blue/green range facilitates circadian phase shifts. This project will test the efficacy of exposure to short-wavelength light for pre-launch and in-flight phase shifting. During eight-day ground-based simulations, researchers will shift participants’ sleep-wake schedules by eight hours. Participants will randomly be placed in groups that receive exposure to either ordinary indoor white light or green light. Participants in each lighting category will be randomly selected to experience either a “gradual” shift or a “slam” shift.

Technical Summary

To synchronize astronauts' circadian sleep-wake schedules to variable launch times, timed exposure to bright light and darkness in the crew quarters during the week-long pre-launch quarantine period has been used since 1990. Although successful at circadian entrainment, bright light protocols are complex to administer and astronauts' compliance is compromised because bright light glare compromises computer/television screen visibility and increases frequency of headaches, irritability and nausea. Moreover, bright light remains unavailable as an in-flight countermeasure, requiring astronauts to rely upon hypnotics or wake-promoting therapeutics to provide symptomatic relief. Recent advances reveal that the human circadian pacemaker is most sensitive to shorter wavelength light for both phase shifting and direct enhancement of alertness and performance. We found that short-wavelength light (~460nm-512nm) in the blue/green range facilitates circadian phase shifting. Therefore, we will test the efficacy of exposure to short wavelength green light at a standard intensity for pre-launch and in-flight phase shifting.

To this end, we will test the circadian phase-shifting efficacy of exposure to short wavelength light throughout scheduled wake times on a protocol designed to simulate the schedule of crew members during the pre-launch quarantine period of a mission that requires an eight-hour phase advance of the sleep-wake schedule. Our goal is to demonstrate that exposure to ambient short wavelength fluorescent light will synchronize human circadian rhythms to a shifted sleep/wake schedule within four-to-five days, enhancing alertness and performance during the biological night.

During this proposed simulation sleep-wake schedules will be advanced by eight hours using three different protocol designs:

A "slam" shift in which the sleep episode is abruptly advanced by eight hours and then maintained for four days,

A gradual shift in which the sleep episode is advanced by 1.6 hours each day for five days until an eight-hour advance is achieved, and

A “slam shift with naps in which the extended wake period prior to theeight-hour advance of the sleep period includes two short nap opportunities.

Given the prolonged extended wake period on the second day of the slam shift schedule the new schedule involves the opportunity to obtain two short naps: one for two hours in the afternoon circadian dip, and the second for four hours at the circadian nadir during the night.

Forty four subjects will be studied in the project. They will be randomized to one of four protocol conditions, which differ by light (ordinary indoor white light [~90 lux] or 90 lux polychromatic green light) and by shift (slam or gradual), so that there will be 11 subjects/group. The four conditions are white light slam shift, green light slam shift, white light gradual shift, and green light gradual shift.

Specific Aims

Test the hypothesis that exposure to ambient polychromatic short wavelength light from fluorescent lamps will be more effective than exposure to an equal illuminance of ambient polychromatic white light from standard fluorescent lamps in shifting the circadian rhythms of test subjects, as measured by dim-light melatonin onset (DLMO), in response to both a gradual eight-hour advance and to an abrupt shift of their sleep-wake schedule.

Test the hypothesis that alertness and neurobehavioral performance in dim light on a constant routine during times at which crew members should be awake on the simulated mission will be significantly greater following four-to-five days of exposure to ambient polychromatic green light versus ambient white light of equal illuminance, due to more effective circadian entrainment.

Test the hypothesis that alertness and neurobehavioral performance will be significantly better on the first night of exposure to ambient polychromatic short wavelength light versus ambient white light of equal illuminance, prior to the induced circadian phase shifts, due to the immediate alerting effects of exposure to ambient polychromatic short wavelength light.

Test the hypothesis that sleep efficiency and total sleep time will be significantly increased and latency to persistent sleep and wake time after sleep onset will be significantly decreased during the sleep episode following four-to-five days of exposure to ambient polychromatic green light versus ambient white light of equal illuminance, due to more effective circadian entrainment.

We predict that exposure to polychromatic green light throughout the day will rapidly entrain the circadian melatonin rhythm to the shifted sleep-wake schedule. We also predict that green light combined with brighter white to prevent the altered color-perception from the green light alone will enable implementation of this new technology to ensure circadian synchronization both during the pre-flight quarantine period and while aboard NASA flight vehicles. We predict that our new schedule with naps will reduce the excessive daytime sleepiness and other adverse effects often experienced with the slam shift due to prolonged wakefulness.

To date, 37 subjects have completed the eight-day protocol. Four subjects completed the white light slam shift condition in order for us to determine the best level of illuminance (90 lux) to be used for both the white and polychromatic green light. To date, 10 subjects have completed the gradual shift protocol, in either white (n=5) or green light (n=5), 21 subjects have completed the slam shift protocol, in either white (n=10) or green light (n=11), and six subjects have completed the combined slam shift with naps protocol. We have completed the third year ahead of schedule for enrollment (11 subjects/year), and anticipate completing the study well in advance of the end of the project period.

Melatonin samples, alertness and performance testing data, and sleep recording data were collected in these studies and are currently being analyzed to address our specific aims. As per a supplemental grant (HPF00003), we implemented novel infra-red technologies into this protocol, and collected data on eye movements in n=30 subjects during periods of extended wake. New eye tracking technologies have also been implemented into the protocol, in order to examine causes of neurobehavioral deficits during periods of extended wake.

Earth Applications

We will be implementing and testing a new polychromatic fluorescent lamp with a peak spectral sensitivity of ~500nm. This is near the peak sensitivity of the human circadian system, and thus should be the most efficacious polychromatic lamp for shifting the timing of the human biological clock. In addition to benefits for NASA flight personnel, this technology will also have application to shiftworkers, jet travelers and any personnel who need to shift the timing of their biological rhythms.